We have developed a "cell growth switch" that allows for the expansion of genetically modified primary hemopoietic cells both in vitro and in vivo. In particular, our f'mdings suggest that this approach may be especially well suited for the expansion of transduced erythroid cells. In view of the latent leukemias that emerged 3 years after gene therapy for X linked SCID, an extensive evaluation of the safety of this approach is warranted. The long-term safety and efficacy of CID administration will be evaluated in specific aim 1. In specific aim 2 we will examine whether CIDs select for integrants adjacent to active genes, as well as potential toxicities associated with gene dosage. In specific aims 3 - 5 we will examine whether the erythropoietin receptor is more favorable for the CID dependent selection of transduced erythroid cells than is mpl. In specific aim 6 we will develop a vector designed to restrict expression of the growth switch to the erythroid lineage. In this manner we will examine both safety and efficacy while taking a deliberate course toward an eventual clinical trial of CID-regulating cell therapy for the inherited red cell disorders.